The aim of the proposed project is to investigate the mechanism by which aldosterone and glucocorticoids modulate monovalent cation transport in the mammalian colon. Recent evidence from my laboratory indicates that glucocorticoid hormones play an important role in maintaining basal cation transport and transmural PD in the mammalian colon. This observation is unprecedented as glucocorticoids have previously been considered to have no effect on electrolyte movement. These studies did not provide a mechanism for the action of glucocorticoids. Glucocorticoids may influence cellular function through an effect on specific glucocorticoid receptor sites or from crossover binding to the aldosterone receptor site. In addition glucocorticoids may have a permissive role in the action of aldosterone. The proposed studies are designed to elucidate the action of both adrenal hormones, aldosterone and glucocorticoids, in the rat colon. Both in vivo colonic perfusion methods and in vitro cation flux studies will be utilized to determine whether the action of the pure glucocorticoid dexamethasone is mediated by similar or separate receptor and effector pathways than those of aldosterone. Ascending and descending colon will be studied separately because of different transport characteristics of these segments. Colonic adrenocorticoid receptors will be identified and their activity correlated with the physiologic effect of each steroid. The effect of glucocorticoids and mineralocorticoids on transtubular gradients will be examined. Metabolic inhibitors will be employed to examine adrenocorticoid transport pathways. The effect of glucocorticoids and mineralocorticoids on luminal permeability and tissue resistance will be examined. Since the colon shares properties in common with all polar epithelia which absorb sodium and secrete potassium it is anticipated that the concepts of hormone action derived from this study will be directly applicable to other target epithelia.